UM171 Expanded Cord Blood In Patients With High-Risk Acute Leukemia/Myelodysplasia

Inclusion Criteria: 1. Presence of high-risk acute leukemia/myelodysplasia defined as one of the following: I. Acute Myeloid Leukemia: 1. Primary induction failure (no CR or CRi after ≥ 2 courses of induction therapy or after ≥ 1 induction containing high dose Ara-C) 2. Chemorefractory relapse (no CR or CRi after 1 chemointensive treatment) 3. Relapse after allogeneic or autologous transplant 4. High risk AML in CR1: i) any adverse genetic abnormality as defined by European Leukemia Net excluding FLT3 mutation; ii) secondary or therapy related AML excluding good risk genetic abnormalities (as defined by ELN); or iii) any other poor risk feature known to be associated with a PFS or DFS ≤40% at 2 years after conventional transplantation. 5. CR2 excluding good risk genetic abnormalities defined by ELN 6. ≥CR3 II. Acute Lymphoid Leukemia 1. Primary induction failure (≥ 2 inductions) 2. Chemorefractory relapse (at least 1 intensive induction chemotherapy; blinatumomab, inotuzumab or CAR-T cells may be considered as an equivalent) 3. Relapse after allogeneic or autologous transplant 4. High risk ALL in CR1: Ph like ALL or any other poor risk feature known to be associated with an PFS or DFS ≤40% at 2 years after conventional transplantation. 5. ≥CR2 6. MRD+ within 1 month of start of conditioning regimen. III. Myelodysplastic syndrome 1. Relapse after allogeneic or autologous transplant 2. ≥10 % blasts within 1 month of start of conditioning regimen 3. Very poor cytogenetics (\>3 abnormalities) 4. Any poor risk feature known to be associated with a PFS or DFS ≤40% at 2 years after conventional transplantation 5. TP53 mutation 6. ≥40 years old and RAS or JAK2 mutation 7. CMML with HCT-specific CPSS score high or intermediate-2 8. Stable disease (absence of CR/PR/HI) after 6 cycles of azacitidine (or another demethylating agent) 9. Progressive disease while on azacitidine (or another demethylating agent) 2. 18-70 years old 3. Availability of 2 CBs ≥ 4/8 HLA match when A, B, C and DRB1 are performed at the allele level. I. Cord to be expanded: 1. CD34+ cell count \>0.5 x 105/kg and TNC\>1.5 x 107/kg (these numbers are all pre-freeze) 2. Needs to be erythrodepleted by bank prior to cryopreservation 3. Must come from a cord bank that is FACT (Foundation for the Accreditation of Cellular Therapy) accredited, FDA approved or eligible for NMDP IND. II. Non-expanded CB/back-up cord: 1. Pre-freeze TNC count ≥ 2.0 x 107/kg with CD34+ cells ≥1.5 x 105/kg or TNC count ≥ 1.5 x 107 TNC/kg with CD34+ cells ≥1.7 x 105/kg. If a single cord does not meet these criteria, 2 back up cords will be an acceptable alternative with a minimum for each of 1.5 x 107/kg TNC and 1 x 105/kg CD34+ cells; another acceptable HSC back up source could be a haploidentical donor with medical clearance prior to starting conditioning regimen. 2. Must come from a cord bank that is FACT accredited, FDA approved or eligible for NMDP IND 4. Karnofsky score ≥ 70% 5. Bilirubin \< 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis; AST and ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN. 6. Estimated or measured creatinine clearance ≥ 60 ml/min/1.73m2. 7. Hematopoietic cell transplantation specific comorbidity index (HCT-CI) ≤5 for patients \< 60 years old; HCT-CI ≤3 for patients \< 60 years old and acute leukemia not in CR/CRi; HCT-CI ≤3 for patients 60-65 years old; HCT-CI ≤1 if 66-70 years old. 8. Left ventricular ejection fraction ≥ 40% 9. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and diffusing capacity corrected for hemoglobin (DLCOc) ≥ 50% of predicted 10. Signed written informed consent 11. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days of enrolment and must be willing to use an effective contraceptive method while enrolled in the study. Exclusion Criteria: 1. Patient never treated with cytotoxic chemotherapy and planned conditioning regimen does not include 12 Gy TBI (exceptions allowed if approved by PI). 2. Allogeneic myeloablative transplant within 6 months. 3. Autologous hematopoietic stem cell transplant within 6 months. 4. Planned use of ATG in conditioning regimen (exceptions allowed if approved by PI in which case ATG must be adjusted for weight/lymphocyte count and given more than 1 week prior to transplant; any patient who receives ATG will have immune recovery studies but will not be counted with rest of patients and will be analyzed separately). 5. Planned use of an HLA matched CB (8/8 allele matched) 6. Uncontrolled infection. 7. Presence of a malignancy other than the one for which the CB transplant is being performed, with an expected survival estimated to be less than 75% at 5 years. 8. Seropositivity for HIV. 9. Hepatitis B or C infection with measurable viral load. Patients with chronic hepatitis B or C infection regardless of viral load require clear documentation of absence of cirrhosis by either fibroscan or biopsy. If fibroscan is the method used, the test must be unequivocally negative. 10. Liver cirrhosis. 11. Active central nervous system involvement 12. Chloroma \> 2 cm 13. ≥50% blasts in marrow in an evaluable marrow sample (\>25% of normal cellularity for age) collected less than one month prior to start of conditioning regimen. 14. Peripheral blasts \>1000/mm3 15. Pregnancy, breastfeeding or unwillingness to use appropriate contraception. 16. Participation in a trial with an investigational agent within 30 days prior to entry in the study. 17. Patient unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and tests. 18. Any abnormal condition or laboratory result that is considered by the PI capable of altering patient's condition or study outcome.